Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis

Objective: The purpose of this study was, to determine the association between active tobacco exposure and aberrant p16 promoter methylation in primary cervical squamous cell cancer and high-grade squamous cervical dysplasia. Study design: p16 methylation-specific polymerase chain reaction was performed on DNA that was extracted from 60 cervical cancers, 30 high-grade dysplasia specimens, and 78 normal cervical cytologic specimens. Patient data were obtained by medical record review or were collected prospectively. Results: Aberrant p16 methylation was significantly higher in squamous cell cervical cancers (61%) than in squamous high-grade dysplasia (20%) or normal cytologic specimens (7.5%). Approximately one half the women with squamous. cancer and one half of the women with high-grade dysplasia were active smokers. Aberrant p16 methylation was associated with active tobacco use in patients with squamous carcinoma (odds ratio, 20.6; 95% CI, 3.6-118; P<;001) and high-grade dysplasia (odds ratio, 4.57; 95% CI, 1.63-12.78; P =.002). Conclusion: Aberrant p16 methylation is associated strongly with active tobacco use in squamous cell cervical cancers and high-grade dysplasia. (C) 2004 Elsevier Inc. All rights reserved.